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生物稳定化人皮肤模块的多模态分析揭示了对注射的mRNA-1273新冠疫苗的协同生态系统反应。

Multimodal profiling of biostabilized human skin modules reveals a coordinated ecosystem response to injected mRNA-1273 COVID-19 vaccine.

作者信息

Scholaert Manon, Peries Mathias, Braun Emilie, Martin Jeremy, Serhan Nadine, Loste Alexia, Bruner Audrey, Basso Lilian, Chaput Benoît, Merle Eric, Descargues Pascal, Pagès Emeline, Gaudenzio Nicolas

机构信息

Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) INSERM UMR1291-CNRS UMR5051, University Toulouse III, Toulouse, France.

Genoskin SAS, Toulouse, France.

出版信息

Allergy. 2024 Dec;79(12):3341-3359. doi: 10.1111/all.16273. Epub 2024 Aug 19.

Abstract

BACKGROUND

The field of drug development is witnessing a remarkable surge in the development of innovative strategies. There is a need to develop technological platforms capable of generating human data prior to progressing to clinical trials.

METHODS

Here we introduce a new flexible solution designed for the comprehensive monitoring of the natural human skin ecosystem's response to immunogenic drugs over time. Based on unique bioengineering to preserve surgical resections in a long survival state, it allows for the first time a comprehensive analysis of resident immune cells response at both organ and single-cell levels.

RESULTS

Upon injection of the mRNA-1273 COVID-19 vaccine, we characterized precise sequential molecular events triggered upon detection of the exogenous substance. The vaccine consistently targets DC/macrophages and mast cells, regardless of the administration route, while promoting specific cell-cell communications in surrounding immune cell subsets.

CONCLUSION

Given its direct translational relevance, this approach provides a multiscale vision of genuine human tissue immunity that could pave the way toward the development of new vaccination and drug development strategies.

摘要

背景

药物研发领域正在见证创新策略的显著激增。在进入临床试验之前,需要开发能够生成人体数据的技术平台。

方法

在此,我们引入一种新的灵活解决方案,用于全面监测天然人类皮肤生态系统对免疫原性药物随时间的反应。基于独特的生物工程技术,可将手术切除组织长期保存于存活状态,首次实现了在器官和单细胞水平对驻留免疫细胞反应的全面分析。

结果

注射mRNA-1273新冠疫苗后,我们对检测到外源物质时引发的精确序列分子事件进行了表征。无论给药途径如何,该疫苗始终靶向树突状细胞/巨噬细胞和肥大细胞,同时促进周围免疫细胞亚群中的特定细胞间通讯。

结论

鉴于其直接的转化相关性,这种方法提供了真实人体组织免疫的多尺度视角,可为新疫苗和药物研发策略的发展铺平道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1baa/11657073/af7f0ed4721d/ALL-79-3341-g001.jpg

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